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Association of CD11b + Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Subhi, Yousif ; Krogh Nielsen, Marie ; Molbech, Christopher Rue ; Krüger Falk, Mads ; Singh, Amardeep LU ; Hviid, Thomas Vauvert Faurschou ; Nissen, Mogens Holst and Sørensen, Torben Lykke (2019) In JAMA Ophthalmology 137(5). p.515-522
Abstract


Importance: CD11b
+
immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b
+
circulating monocytes is associated with the number of anti-vascular endothelial growth factor... (More)


Importance: CD11b
+
immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b
+
circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Design, Setting, and Participants: These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Exposures: Proportion of CD11b
+
circulating monocytes. Main Outcomes and Measures: The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b
+
circulating monocytes and the correlation between these values. The angiogenic role of CD11b
+
circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Results: Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b
+
monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P =.004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P =.002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P =.005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P =.004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P =.002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P <.001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P =.30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P =.02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P =.005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b
+
monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Conclusions and Relevance: Results of this study demonstrated that the proportion of circulating CD11b
+
monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy..

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA Ophthalmology
volume
137
issue
5
pages
515 - 522
publisher
American Medical Association
external identifiers
  • pmid:30844038
  • scopus:85062646071
ISSN
2168-6165
DOI
10.1001/jamaophthalmol.2019.0010
language
English
LU publication?
yes
id
d9ee8d24-f002-4112-9686-33d6108fee57
date added to LUP
2019-03-19 12:31:58
date last changed
2019-12-10 07:59:05
@article{d9ee8d24-f002-4112-9686-33d6108fee57,
  abstract     = {<p><br>
                                                         Importance: CD11b                             <br>
                            <sup>+</sup><br>
                                                          immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b                             <br>
                            <sup>+</sup><br>
                                                          circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Design, Setting, and Participants: These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Exposures: Proportion of CD11b                             <br>
                            <sup>+</sup><br>
                                                          circulating monocytes. Main Outcomes and Measures: The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b                             <br>
                            <sup>+</sup><br>
                                                          circulating monocytes and the correlation between these values. The angiogenic role of CD11b                             <br>
                            <sup>+</sup><br>
                                                          circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Results: Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b                             <br>
                            <sup>+</sup><br>
                                                          monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P =.004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P =.002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P =.005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P =.004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P =.002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P &lt;.001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P =.30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P =.02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P =.005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b                             <br>
                            <sup>+</sup><br>
                                                          monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Conclusions and Relevance: Results of this study demonstrated that the proportion of circulating CD11b                             <br>
                            <sup>+</sup><br>
                                                          monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy..                         <br>
                        </p>},
  author       = {Subhi, Yousif and Krogh Nielsen, Marie and Molbech, Christopher Rue and Krüger Falk, Mads and Singh, Amardeep and Hviid, Thomas Vauvert Faurschou and Nissen, Mogens Holst and Sørensen, Torben Lykke},
  issn         = {2168-6165},
  language     = {eng},
  number       = {5},
  pages        = {515--522},
  publisher    = {American Medical Association},
  series       = {JAMA Ophthalmology},
  title        = {Association of CD11b                         
                        <sup>+</sup>
                                                  Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy},
  url          = {http://dx.doi.org/10.1001/jamaophthalmol.2019.0010},
  doi          = {10.1001/jamaophthalmol.2019.0010},
  volume       = {137},
  year         = {2019},
}